Delayed combinatorial treatment with flavopiridol and minocycline provides longer term protection for neuronal soma but not dendrites following global ischemia

Journal of Neurochemistry
Grace O IyirhiaroDavid S Park

Abstract

We previously reported that delayed administration of the general cyclin-dependent kinase inhibitor flavopiridol following global ischemia provided transient neuroprotection and improved behavioral performance. However, it failed to provide longer term protection. In the present study, we investigate the ability of delayed flavopiridol in combination with delayed minocycline, another neuroprotectant to provide sustained protection following global ischemia. We report that a delayed combinatorial treatment of flavopiridol and minocycline provides synergistic protection both 2 and 10 weeks following ischemia. However, protected neurons in the hippocampal CA1 are synaptically impaired as assessed by electrophysio logical field potential recordings. This is likely because of the presence of degenerated processes in the CA1 even with combinatorial therapy. This indicates that while we have addressed one important pre-clinical parameter by dramatically improving long-term neuronal survival with delayed combinatorial therapy, the issue of synaptic preservation of protected neurons still exists. These results also highlight the important observation that protection does not always lead to proper function.

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Citations

Apr 23, 2010·Molecular Neurobiology·Robert Piotr StrosznajderJoanna Benigna Strosznajder
Jun 16, 2009·Neurotoxicity Research·Bogdan A StoicaAlan I Faden
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May 16, 2014·The Journal of Biological Chemistry·Grace O IyirhiaroDavid S Park
Feb 22, 2012·Antioxidants & Redox Signaling·Alexander A MonginDavid Jourd'heuil
Dec 17, 2020·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Zhanyang YuXiaoying Wang
Sep 5, 2017·Neuropharmacology·Poornima VenkatJieli Chen

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